Newcastle disease virus (NDV) is an avian virus causing a contagious bird disease affecting many domestic and wild avian species. Exposure of humans to infected birds (e.g., in poultry processing plants) can cause mild conjunctivitis and influenza-like symptoms, but NDV otherwise poses no hazard to human health and most people are seronegative for NDV. Based on viral pathogenicity in chickens, NDV pathogenicity is classified as high (velogenic), medium (mesogenic) or low (lentogenic) as determined by the intracerebral pathogenicity index (ICPI). Due to agricultural concerns, the mesogenic and velogenic NDV having chicken virulence (ICPI>0.7) have been classified by the USDA as “select agents” since 2008. The Select Agents and Toxin List includes biological agents having the potential to pose a severe threat to human and animal health, to plant health, or to animal and plant products
Naturally occurring forms of NDV have been used in clinical studies as an immunotherapeutic and virotherapeutic biologic. NDV shows promise as an anticancer agent because of the virus' ability to selectively kill human tumor cells with limited toxicity to normal cells. However, due to the reclassification of NDV as a select agent, the development of NDV as an anti-cancer agent has failed to progress. Other oncolytic viruses have shown considerable promise in clinical trials. To facilitate the development of NDV as a cancer therapy, new forms of the virus are required. Ideally, such new forms would retain their ability to target tumor cells, but would no longer cause disease in birds.